MHC class II engagement in brain endothelial cells induces protein kinase A-dependent IL-6 secretion and phosphorylation of cAMP response element-binding protein
S. Etienne et al., MHC class II engagement in brain endothelial cells induces protein kinase A-dependent IL-6 secretion and phosphorylation of cAMP response element-binding protein, J IMMUNOL, 163(7), 1999, pp. 3636-3641
Activated endothelial cells can directly participate in immune responses by
interacting with immunocompetent cells via class II MHC proteins. We show
here that, after induction of MHC class II molecule expression by IFN-gamma
, rat brain endothelial cells responded to MHC class II ligands, anti-MHC c
lass II Abs, or superantigens by expression of IL-6 transcript and IL-6 sec
retion. This response was not affected by protein kinase C depletion but wa
s mimicked by the cAMP-elevating agent forskolin and completely blocked by
H89, an inhibitor of cAMP-dependent protein kinase (PKA), Involvement of a
cAMP/PKA signaling pathway in response to MHC class II ligands was further
demonstrated by measure of a dose-dependent increase in cAMP level and phos
phorylation of the transcription factor cAMP response element-binding prote
in (CREB), Our results indicate that MHC class II engagement in brain endot
helial cells is directly coupled to IL-6 production via a cAMP/PKA-dependen
t intracellular pathway.